332 RIBOFLAVIN 



They were found to be devoid of antimalarial activity and did not show 

 the tendency to inhibit the metabolic effects of riboflavin. 9-(/3-Diethyl- 

 aminoethyl)isoalloxazine hydrochloride was ineffective in mice infected 

 with Trypanosoma nagana}^^ 



Summary. The preceding discussions show that only slight changes in the 

 chemical constitution of riboflavin can be made without loss of vitamin B2 

 activity. This fact is in agreement with the high chemical specificity of vi- 

 tamins in general. In replacing the ribityl side chain by other sugar alcohols, 

 or by alteration of substituents in the benzene ring of the isoalloxazine 

 nucleus, derivatives can be obtained which are antagonists of riboflavin. 



No derivatives of flavins effective against pathogenic organisms have yet 

 been developed but carcinolytic activity was found among chloro-D-sorb- 

 oflavins. 



III. Industrial Preparation 



THEODOR WAGNER-JAUREGG 



Pure crystallized riboflavin for therapeutic purposes is made by chemical 

 synthesis. It is difficult to indicate actual manufacturing processes, since 

 they are held as confidential. The best index of determining the methods 

 used in the industry is the patent literature.^ 



Concerning the pentose component, methods of riboflavin synthesis with- 

 out the use of D-ribose are of interest, since none of the known syntheses 

 of D-ribose are simple and economical. Different syntheses of N-(D-ribityl)- 

 3,4-dimethylaniline, the key intermediate in the riboflavin synthesis, have 

 been developed which do not involve D-ribose (p. 318). The introduction 

 of the second amino group can be performed with good yield by the method 

 of Karrer and Meerwein (p. 317). 



With regard to the isoalloxazine formation, different patented methods 

 have been described : (1) requisite diamine and alloxan; (2) requisite amino- 

 azo compound and barbituric acid;^ (3) requisite aminoazo compound and 

 dialluric acid in the presence of a hydrogen transfer catalyst (in this method, 

 reduction to the diamine occurs) ; (4) requisite diamine and dichlorobarbitu- 

 ric acid. Examples have been given in the preceding section (pp. 315ff.). 



Vitamin B2 concentrates suited to enrich poultry and livestock feeds can 

 be prepared more cheaply by fermentation processes. During World War 



• A list of patents on vitamin Bo can be found in H. Vogel and H. Knobloch, Chemie 

 uud Technik der Vitamine, 3rd ed., Vol. 2, Issues 1 and 2, pp. 197-214. Ferdinand 

 Enke, Stuttgart, 1953. 



2M. Tishler, K. Pfister, 3rd, R. D. Babson, K. Ladenburg, and A. J. Fleming, 

 J. Am. Chem. Soc. 69, 1487 (1947). 



